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  • Title: [Teratogenic and mutagenic risks of radiotherapy: when and how to prescribe contraception].
    Author: Marty M, Mignot L, Gisselbrecht G, Morvan F, Gorins A, Boiron M.
    Journal: Contracept Fertil Sex (Paris); 1985 Jan; 13(1 Suppl):181-6. PubMed ID: 12280202.
    Abstract:
    The increasing potential for curing cancer in young patients poses problems of contraceptive choice and pregnancy planning for these patients. Chemotherapy instead of surgical removal of some tumors may allow preservation of reproductive function. The ovary is highly sensitive to radiation; the degree of sensitivity depends on the dose received and the age of the patient. If ovarian function is maintained or regained, the subsequent teratogenic risk appears to be minimal although the incidence of spontaneous abortion is increased. The testicle is even more radiosensitive than the ovary, but the later mutagenic or chemotherapeutic risk appears small. The majority of anticancer chemotherapeutic agents have a mutagenic potential as demonstrated by the Ames test. The impact of chemotherapy on the ovary is gauged by effects on the menstrual cycle, the possibility of later pregnancy, and hormonal levels. Clinical manifestations of ovarian effects include amenorrhea, signs of estrogen insufficiency, and elevated serum follicle stimulating hormone and luteinizing hormone levels. The most gonadotoxic are the alkylating agents, methyl donors, and intercalating agents, with antimetabolites apparently less toxic. Continuous or high dose administration results in higher toxicity, as does administration of a combination of drugs. The effects of chemotherapy depend on age and indirectly on the type of cancer. It is not yet possible to quantify the risk of precocious menopause after chemotherapy. The risk from fetal exposure to ionizing radiation is greatest during the 1st 16 weeks of embryonic life. After the organs are formed, risks of retarded growth or of cancer in the infant continue to be significant. Numerous cytotoxic agents are known to have abortifacient or teratogenic effects in animals, but extrapolation of experimental results to humans is difficult. Exposure during the 1st trimester involves a significant risk of fetal anomaly although normal births have occurred after monochemotherapy. The teratogenic risk appears to be small following mono- or polychemotherapy in the 2nd or 3rd trimester, but longterm carcinogenic risks are unknown. The risk of fetal anomalies in pregnancies begun after maternal anticancer treatment appears to increase with maternal age at treatment, total dose of anticancer agents, use of a combination of drugs, the duration of treatment, simultaneous radiation treatment, and the shortness of the time elapsed since treatment. Effective contraception should be practiced during cancer treatment, and pregnancy, if not contraindicated, should not be attempted until 2 years after treatment. No prospective studies have been done on contraceptive indications for cancer patients. Oral contraceptives containing estrogen are logically contraindicated for women with estrogen dependent tumors, which for premenopausal women would be limited to breast cancer. Contraindications for IUDs are more broad and depend on the type of anticancer therapy, with intensive polychemotherapy entailing risks of hemorrhage and infection a strong contraindication.
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